FDA Approves First-in-Class Drug for Gastric Cancer

The FDA has approved Vyloy (zolbetuximab-clzb) as a first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. It is indicated to be used in combination with fluoropyrimidine- and platinum-containing chemotherapy.

In the United States, it is estimated that 26,890 people will be diagnosed with gastric cancer and 10,880 will die from the disease in 2024. These cancers are often diagnosed in the advanced or metastatic stage. The five-year relative survival rate for patients at the metastatic stage is 7%.

“While there have been advances in the first-line treatment of locally advanced unresectable and metastatic gastric and GEJ cancers in the last several years, there is still a tremendous unmet need among our patients,” Samuel J. Klempner, M.D., associate professor, Harvard Medical School, Medical Oncologist at Massachusetts General Hospital, Boston, said in a news release.

Developed by Astellas, Vyloy is a first-in-class monoclonal antibody that targets and binds to Claudin 18.2 (CLDN18.2), a transmembrane protein. Transmembrane proteins are involved in signal transduction, transport, and protein trafficking, and a study published last year indicated these proteins may contribute to the spread of cancer. Vyloy acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells, which then leads to cancer cell death by activating two distinct immune system pathways.

Vyloy will be available to order through specialty distributors in about 6-12 business days. The wholesale acquisition cost is $1,600.00 per 100mg vial. A spokesperson said the number of treatments could vary per patient. Individual treatment costs per patient will vary based on a patient’s weight, height and duration of therapy.

Astellas is offering a copay program for $5 per dose. The program has an annual limit of $25,000 per calendar year. The terms of the copay assistance state: “the benefit is not valid for any other out-of-pocket costs such as medication administration charges or other healthcare provider services. No other individual or entity (including, without limitation, third party payers, pharmacy benefit managers, or the agents of either) is entitled to receive any benefit, discount, or other amount in connection with this program.

A spokesperson said the company expects Vyloy to be covered by a wide range of commercial and Medicare plans, under the patient's medical benefit. They expect a standard prior authorization based on the label. About 50% of patients in the United States are expected to be Medicare beneficiaries.

The approval is based on results from the phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated Vyoy plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared with placebo plus mFOLFOX6. The GLOW study evaluated Vyloy plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared with placebo plus CAPOX.

Both trials met their primary endpoint, progression-free survival, as well as a key secondary endpoint, overall survival. The most common all-grade treatment-emergent adverse events reported in the Vyloy treatment arms were nausea, vomiting and decreased appetite.2,

The FDA also Ventana CLDN18 RxDx Assay from Roche, a test to identify patients who may be eligible for treatment with Vyloy.